Drug Interactions Flashcards
Definition of drug interaction
Administration of one agent that modifies effect of a drug
5 agents that can cause drug interaction
pharma. drug recreational drug environmental toxin food herbals
3 types of drug interactions
Pharmaceutical
Pharmacokinetic
Pharmacodynamic
When do pharmaceutical drug interactions happen?
Interactions occur prior to administration
Example of pharmaceutical drug interaction
Penicilin (-) and Aminoglycoside (+) make an insoluble precipitate
Pharmacokinetic drug interactions is due to a change of what?
Concentration in target tissue
Pharmacodynamic drug interactions alter what?
How tissue responds to drug in presence of agent
3 ways to prevent drug interaction
- Understand Drug mechanism
- Monitor blood levels of drugs with narrow therapeutic index
- Monitor parameters that may help characterize the early events of an interaction or toxicity
3 different pharmacodynamic interactions?
Same target
Same pathway
Complement pathway
In PK, drug interactions affect what?
Absorption (bioavailability)
Distribution
Metabolism (elimination)
Excretion (elimination)
The most pronounced PK drug interactions are those that affect ____________ and _______________
bioavailability and elimination
Absorption of drugs may be affected by concurrent use of other agents that…? (3)
- Bind or chelate
- Alter GI physiology
- Alter gut bacteria (enterohepatic circulation)`
What does cholestyramine do for hyperlipidemia?
In hyperlipidemic patients, cholesterol is precursor of bile salts in the intestines, but then gets reabsorbed into the liver.
Cholestyramine binds to salts and bile acids preventing the reabsorption from the intestines
Which drugs does cholestyramine bind with? (3) When should they be given if given together?
Digoxin
Warfarin
Tetracyclines
Drug should be given 1-2 hours before (or 4-6h after) cholestyramine
GI motility : what happens to absorption in a short vs. long transit time of food?
Short : incomplete absorption
Long : may delay absorption if it slows gastric emptying, may increase total absorption
What can increase transit time of food? (2)
Large meals and some drugs (morphine)
What can decrease transit time of food? (2)
Fasting
Laxatives
Ionized weak acid/bases : do they cross membranes easier or harder than nonionized?
harder
The protonated form of weak acid/bases is at lower or higher pH?
Lower
Is the protonated form of weak acids ionized or nonionized?
Nonionized
Is the protonated form of weak bases ionized or nonionized?
Ionized
Role of antacids? How does that affect the absorption of drugs that are weak acids/bases?
Increase gastric pH
Acids : decreases absorption
Bases : Increases absorption
Distribution of drugs can be altered by agents that…? (2)
Compete for plasma protein binding or tissue binding
Alter barrier function
3 drugs that are highly bound to plasma proteins and affect distribution?
Phenytoin
Tolbutamide for T2D
Warfarin
Which drugs can reverse binding to plasma proteins and increase distribution?
Aspirin
Sulfonamides
2 things that can reduce oral bioavailability, affecting GI metabolism and transport?
Elimination of these increases or decreases bioavailability?
Drug transporters (PGP) Metabolizing enzymes (CYP3A4)
Increases
What food can inhibit cYP3A4 and PGP?
Naringin in citrus juices
How many drugs are known to inhibit CYP3A4 and PGP?
85
What is the affect of agents on barrier function?
Can inhibit efflux transporters (PGP) at barrier tissues and increase tissue bioavailability
2 antifunguals that inhibit CYP3A4?
Itraconazole
Fluconazole
Why are CYP3A4 inhibitors more efficient given orally than by IV? (2)
It goes through the enterohepatic pathway
CYP3A4 is in the epithelial cells of the GI tract
Agents can have which effects on drug metabolizing enzymes?
Inhibit
Induce
Two types of inhibition? How does this affect the binding?
Reversible : two agents compete for the active site of enzyme
Irreversible : bind with another agent rendering enzyme inactive
CYP3A IRREVERSIBLE inhibitor has longer or shorter effect vs. reversible inhibitor? Delayed or faster effect?
Longer
Delayed
What can increase gene expression of drug metabolizing enzymes? (2)
Many drugs
St. John’s wort
What is the active ingredient in St. John’s wort?
Hyperforin
Hyperforin and rifampicin :
- Activates what transcriptional regulator of CYP3A4?
- increase or decrease expression of CYP3A4?
- Does it increase or decrease drugs that are metabolized by CYP3A4?
PXR
Increase
Decrease
Agents that can inhibit hepatic and renal drug transport can reduce what.
Can this become toxic? how?
drug elimination (increases half-life) Yes, depending on the site of interaction
Example of transporter interaction?
Penicillin was needed during WWII.
Probenecid inhibits renal penicillin transport so they used that for the penicillin concentration to last longer
What can affect urinary pH? This also influences what?
Drugs
Diet
Also influences renal excretion of weak acids and bases
What happens to absorption of weak acids/bases when there is an alkaline pH?
increases reabsorption of weak bases
decrease reabsorption of weak acids
Drugs are concentrated in ________ due to water absorption
Distal nephron
Drugs that are nonionized are most likely to be reabsorbed ______
passively
